Sensory hair cells are responsible for detecting and transmitting sound in the inner ear,and damage to HCs leads to hearing loss.HCs do not regenerate spontaneously in adult mammals,which makes the hearing loss perman...Sensory hair cells are responsible for detecting and transmitting sound in the inner ear,and damage to HCs leads to hearing loss.HCs do not regenerate spontaneously in adult mammals,which makes the hearing loss permanent.However,hair cells and supporting cells have the same precursors in the inner ear,and in newborn mice,the adjacent SCs can be activated by gene manipulation to differentiate into newly regenerated hair cells.Here,we demonstrate the role of the Ras association domain family member 2(Rassf2)in supporting cell to hair cell trans-differentiation in the inner ear.Using the AAV vector(AAV-ie)to upregulate Rassf2 expression promoted supporting cell division and hair cell production in cultured cochlear organoids.Also,AAV-Rassf2 enhanced the regenerative ability of Lgr5+SCs in the postnatal cochlea without impairing hearing,and this might due to the modulation of the Wnt,Hedgehog and Notch signaling pathways.Furthermore,AAV-Rassf2 enhances cochlear supporting cell division and hair cell production in the neomycin injury model.In summary,our results suggest that Rassf2 is a key component in HC regenerative repair,and gene modulation mediated by adeno-associated virus may be a promising gene therapy for hearing repair.展开更多
The cochlea consists of multiple types of cells,including hair cells,supporting cells and spiral ganglion neurons,and is responsible for converting mechanical forces into electric signals that enable hearing.Genetic a...The cochlea consists of multiple types of cells,including hair cells,supporting cells and spiral ganglion neurons,and is responsible for converting mechanical forces into electric signals that enable hearing.Genetic and environmental factors can result in dysfunctions of cochlear and auditory systems.In recent years,gene therapy has emerged as a promising treatment in animal deafness models.One major challenge of the gene therapy for deafness is to effectively deliver genes to specific cells of cochleae.展开更多
Dear Editor,Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)has caused the COVID-19 pandemic,with more than 528 million infections and 6.2 million deaths.To fight against this rapidly spreading pandemic,pro...Dear Editor,Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)has caused the COVID-19 pandemic,with more than 528 million infections and 6.2 million deaths.To fight against this rapidly spreading pandemic,prophylactic vaccines have been developed using different techniques,such as inactivated virus,messenger RNAs,recombinant proteins,and viral-vectored vaccines.However,rapidly spreading variants of SARS-CoV-2,such as alpha,beta,delta,and omicron variants,have been emerging.展开更多
基金supported by the National Key Research and Development Program of China (2021YFA1101300,2020YFA0112503,2021YFA1101800 and 2020YFA0113600)the National Natural Science Foundation of China (81970882,82030029,92149304,82000984 and 82171146)+6 种基金the China National Postdoctoral Program for Innovative Talents (BX20200082)the China Postdoctoral Science Foundation (2020M681468)the Science and Technology Department of Sichuan Province (2021YFS0371)the Shenzhen Fundamental Research Pro-gram (JCYJ20190814093401920 and JCYJ20210324125608022)the Open Research Fund of State Key Laboratory of Genetic Engineering,Fudan University (SKLGE-2104)2022 Open Project Fund of Guangdong Academy of Medical Sciences to P.N.W. (YKY-KF202201)Key Program of Zhejiang Provincial Natural Science Foundation of China (LZ22H130001).
文摘Sensory hair cells are responsible for detecting and transmitting sound in the inner ear,and damage to HCs leads to hearing loss.HCs do not regenerate spontaneously in adult mammals,which makes the hearing loss permanent.However,hair cells and supporting cells have the same precursors in the inner ear,and in newborn mice,the adjacent SCs can be activated by gene manipulation to differentiate into newly regenerated hair cells.Here,we demonstrate the role of the Ras association domain family member 2(Rassf2)in supporting cell to hair cell trans-differentiation in the inner ear.Using the AAV vector(AAV-ie)to upregulate Rassf2 expression promoted supporting cell division and hair cell production in cultured cochlear organoids.Also,AAV-Rassf2 enhanced the regenerative ability of Lgr5+SCs in the postnatal cochlea without impairing hearing,and this might due to the modulation of the Wnt,Hedgehog and Notch signaling pathways.Furthermore,AAV-Rassf2 enhances cochlear supporting cell division and hair cell production in the neomycin injury model.In summary,our results suggest that Rassf2 is a key component in HC regenerative repair,and gene modulation mediated by adeno-associated virus may be a promising gene therapy for hearing repair.
基金This work was supported in part by the Hundred Talent Program of Guangzhou University and the National Natural Science Foundation of China （31501178）, as well as by the ＇Strategic Priority Research Program＇ of the Chinese Academy of Sciences （XDA16020501 and XDA16020404）, the National Key Basic Research and Development Program of China （2017YFA0102700, 2015CB964500, and 2014CB964804）, and the National Natural Science Foundation of China （31661143042, 91519314, 31630043, 31571513, and 31430058）.
基金We thank the Shanghai Municipal Government and ShanghaiTech University,and the Bioimaging Core Facilities of the iHuman Institute and the animal facility of National Center for Protein Science Shanghai for their financial support.Hao Wu was supported by the Key Project of the National Natural Science Foundation of China(NSFC 81730028)the National Key Technology Research and Development Program of the Ministry of Science and Technology of China(2017YFC1001800)+4 种基金Shanghai Key Laboratory of Translational Medicine on Ear and Nose diseases(14DZ2260300)Shanghai Municipal Science and Technology Major Project(2018SHZDZX05)the Innovative Research Team of High-level Local Universities in Shanghai.This work was supported by the National Natural Science Foundation of China(31771130(G.Z.)the 2015 Thousand Youth Talents Plan of China(G.Z.,).This work was supported by the National Natural Science Foundation of China(82122019,Y.T.)the program for professors with special appointments(Eastern Scholar,Y.T.)at Shanghai Institutions of Higher Learning.
文摘The cochlea consists of multiple types of cells,including hair cells,supporting cells and spiral ganglion neurons,and is responsible for converting mechanical forces into electric signals that enable hearing.Genetic and environmental factors can result in dysfunctions of cochlear and auditory systems.In recent years,gene therapy has emerged as a promising treatment in animal deafness models.One major challenge of the gene therapy for deafness is to effectively deliver genes to specific cells of cochleae.
基金supported by Science and Technology Commission of Shanghai Municipality(YDZX20223100001002)Shanghai Frontiers Science Center for Biomacromolecules and Precision Medicine at ShanghaiTech University,Shanghai Local College Capacity Building Project(22010502700)+1 种基金grants from the National Key Research and Development Program of China(2017YFC1001301(G.Z.),2019YFA0111000(H.W.))National Natural Science Foundation of China(31871487(C.L.)).
文摘Dear Editor,Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)has caused the COVID-19 pandemic,with more than 528 million infections and 6.2 million deaths.To fight against this rapidly spreading pandemic,prophylactic vaccines have been developed using different techniques,such as inactivated virus,messenger RNAs,recombinant proteins,and viral-vectored vaccines.However,rapidly spreading variants of SARS-CoV-2,such as alpha,beta,delta,and omicron variants,have been emerging.
